The Respiratory System
4.1.5 Control of Coordinated Laryngeal and Pump Muscle
interrupted briefly by laryngeal closure. This mechanism may reset vagal afferent feedback, avoiding a Hering–Breuer inflation reflex and possible loss of the acquired volume (see Sect.
47.3.1). In summary, human and animal data emphasize the importance of laryngeal control of expiratory subglottic airway volume. This central control strategy whereby airway pressure is dependent upon volume control has been shown by the study of bubble physics to produce a more stable mechanical system (Hildebrandt 1974). Thus, coordinated central control of
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protective responses, including swallowing, apnea, obstructed respiratory efforts, cough, hypertension, and arousal from sleep (Thach 2008). An obstructive apnea with bradycardia results if the LCR stimulus is persistent, espe- cially in the immature or depressed brain. This LCR response alters with age – coughing becomes the major response. However, acquisi- tion of a viral infection in infancy can rekindle its potency (Thach 2008). It is augmented by hypox- emia and anemia and has been implicated in apnea of prematurity and SIDS (Thach 2008) (see Sect. 47.3.1).
Other laryngeal SLN afferents, including those from mechanoreceptors, drive receptors, and temperature receptors, affect laryngeal intrin- sic muscle activities. Although SLN section does not alter the eupneic breathing pattern, these afferents are important. Upper airway bypass can alter the inspiration-inhibition Hering–Breuer reflex. Application of acid to the larynx in ani- mals, mimicking chronic aspiration, alters the subsequent response to an applied airway load (see Sect. 47.3.1). During noninvasive ventila- tion, nonsynchronous delivery of airflow to the upper airway in neural expiration results in laryn- geal closure (Rodenstein 2004; Scharf et al.
1978). Thus, noninvasive ventilation and pacing of a paralyzed diaphragm should be applied syn- chronously with neural inspiration (Rodenstein 2004; Scharf et al. 1978).
In intact animals, compensatory glottic abduc- tion follows single-breath total occlusion of inspi- ration or expiration at the mouth/nose. During the unimpeded expiration following a single inspira- tory occlusive load, unopposed TA activity can produce laryngeal closure. Thus when no air enters the lung, a compensatory reflex mechanism can prevent expiratory volume loss, maintaining absolute subglottic volume. Lower airway affer- ent inputs affect glottic size (Bailey and Fregosi 2006). Stretch receptor discharges, induced by PEEP, decrease expiratory TA activity (Harding 1986). By contrast increased expiratory glottic adduction follows rapidly adapting receptor stim- ulation, e.g., with deflation or irritant stimulation secondary to a pneumothorax (Bartlett 1989), or follows C-fiber stimulation, e.g., with experimen- tal pulmonary edema (Bartlett 1989). Direct and
indirect stimulation of chest wall muscle afferents can invoke several flow patterns involving glottic closure (Bartlett 1989; Stecenko and Hutchison 1991).
While pseudoasthma can be fabricated by par- tial glottic closure (Rodenstein 2004), matching laryngeal control of flow pattern to maintain opti- mal subglottic airway volume may explain changes reported with true increased airway resistance. Subglottic inspiratory flow limitation in croup is associated with expiratory flow resis- tance, probably glottic in origin (Argent et al.
2008). Increased lower airway resistance in adult asthmatic patients induces a breathing pattern characterized by laryngeal expiratory flow retar- dation (Collett et al. 1983; Sekizawa et al. 1987).
In adults, resistive loads applied at the mouth also decrease expiratory glottic size (Brancatisano et al. 1985). This change may occur immediately, suggesting that resistive loading, unlike total occlusive (elastic) loading, produces sudden flow changes that stimulate airway receptors to cause laryngeal adduction (Brancatisano et al. 1985).
Therapy with CPAP reverses the expiratory laryngeal adduction in some asthmatic subjects, suggesting that airway pressure changes may alter the dynamics between stretch receptor and irritant receptor stimulations, thus changing the breathing pattern (Collett et al. 1983). In normal adults a voluntary deep breath can decrease laryngeal resistance and lower airway resistance (Sekizawa et al. 1987). By contrast, bronchocon- strictive stimulation in normal adults can result in inspiratory and expiratory glottic narrowing (Higenbottam 1980). An increased resistance to inspiratory flow may be advantageous in that more transpulmonary pressure is applied to open- ing a constricted peripheral airway. If lower air- way volume and resistance changes affect laryngeal function, can absence of laryngeal control affect lower airway resistance? Laryngeal bypass during invasive ventilation is associated with atelectasis and with the development of increased lower airway resistance (Hutchison and Bignall 2008). The latter effect may stiffen the conducting airways and thus stabilize total airway volume but demand increased effort. In summary, the data reflect the importance of laryngeal subglottic volume control as a
Pediatric and Neonatal Mechanical Ventilation
determinant of lower airway resistance and point to interactions between lower airway afferents and coordinated laryngeal and pump muscle activities in this dynamic process (see also Sect.
47.3.1).
4.1.5.2 Central and Chemical Control Central control of coordinated laryngeal and dia- phragmatic muscle activities is determined by developmental stage, behavioral states, metabo- lism (temperature), central inputs, and centrally acting chemicals. Postnatally in lambs, increased expiratory TA activity with decreased PCA activ- ity occurs during the NREM state. By contrast, expiratory TA activity in REM is mainly absent, while PCA activity is variable (Harding 1986). In normal adult humans, expiratory TA activity is absent during stable NREM, while expiratory PCA activity decreases in NREM and is variable in REM (Kuna et al. 1988, 1990). At all ages, expira- tory TA activity occurs at arousal. Thus behavioral state is a key factor in subglottic airway volume control that, in turn, is important in sleep apnea.
Increased central drive, with hyperventilation and/or hypercapnia, promotes laryngeal abduc- tion in inspiration and expiration in adults and term newborns, in whom increased PCA, dia- phragmatic and intercostal muscle activities occur (Bartlett 1989; Insalaco et al. 1990; Kuna et al. 1994; Wozniak et al. 1993). Laryngeal adduction can occur during hypercapnic hyper- ventilation in preterm neonates, probably due to chest wall distortion (but see also Sect. 47.3.1) (Eichenwald et al. 1993). This adduction also occurs in adults at the mechanical limits of air- way volume (Brancatisano et al. 1983). In gen- eral, however, increased central drive decreases laryngeal resistance unless mechanical limita- tions are present.
Decreased central drive with hypocapnia diminishes expiratory glottic size and is associ- ated with periodic breathing in adults (Kuna et al.
1993; Rodenstein 2004). Laryngeal closure has been noted in human newborns and infants with apnea or suspected apparent life-threatening events (Ruggins and Milner 1991, 1993). During central apnea and periodic breathing in lambs, expiratory TA activity is noted (Praud 1999). In
depressed human infants at birth, laryngeal clo- sure can block intubation, and, in lambs, acute cerebral hypoxia–ischemia results in expiratory TA activity with laryngeal closure (Hutchison et al. 2002). Centrally acting depressant drugs diminish central drive and, in lambs, produce laryngeal closure with apnea (Praud 1999).
In former preterm infants, up to ~55–60 postmen- strual weeks, exposure to anesthesia and/or oper- ative stress can result in apnea postoperatively (see Sect. 47.3.1). Thus, the intensivist should avoid hypocapnia during noninvasive ventilation and be aware that central depression can result in apnea with glottic closure.
Hypoxia stimulates expiratory laryngeal abduction and increases ventilation in human adults and newborn lambs (England et al. 1982b;
Insalaco et al. 1990; Praud et al. 1992). In lambs, the increase in ventilation is dependent upon carotid body input – a sudden decrease in that input induces expiratory TA activity (Praud et al.
1992). However, animal and human data indicate that the effects of carotid body input vary depend- ing upon central state and the presence/absence of other inputs (de Burgh Daly et al. 1979). If animals are vagotomized and paralyzed, direct carotid body stimulation can induce expiratory TA activity, and exposure to hypoxia after air- way vagal blockade or intrathoracic vagal section results in laryngeal adduction (Bailey and Fregosi 2006). In adult humans, the degree of expiratory glottic adduction with hypoxia exceeds that dur- ing hypercapnia (England et al. 1982b). Thus, it is argued that the “pure” carotid body reflex response is laryngeal expiratory adduction that will retain airway volume and promote oxygen- ation. This pure response can be countered by the presence of ventilation which increases air- way stretch receptor feedback that results in an overall expiratory laryngeal abduction response.
In the author’s view, a unifying explanation for the diverse findings with hypoxia is that the effect of carotid body input is to augment the central coordinated output to laryngeal and pump mus- cles that is selected under different conditions (see Sect. 47.3.1). When central depression exists, protective inputs and/or absence of vol- ume-related inputs produce an apneic response
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with glottic closure that is augmented by hypoxia.
This can be seen in the “vagal” preterm infant who is sedated for a surgical procedure. At intu- bation laryngeal closure and apnea/bradycardia can be triggered. If hypoxemia ensues, the prob- lems are aggravated. When tidal ventilation and airway volume feedback are restored, the impact of any ongoing hypoxemia is to augment breath- ing. Hering and Breuer found that their volume- related reflexes were active even with hydrogen breathing. This fits the modern focus on ventila- tion for resuscitation from asphyxia.
Conclusion
This chapter of upper airway physiology for the pediatric intensivist has focused on motor and specifically on laryngeal aspects relevant to the control of breathing patterns. The major message is that upper airway physiology is involved in all aspects of “breathing”: protec- tion, volume homeostasis, and ventilation; its functional impact covers the entire airway, from the nose to the alveolus. Understanding upper airway physiology can guide and improve therapy, while therapy can aid a return to normal homeostasis or detract from it. Current knowledge of upper airway physi- ology has had major implications for the application of invasive and noninvasive venti- latory support. Much remains to be learned from the interactions between physics and biochemistry in the entire airway and how they affect breathing patterns.
Acknowledgements The author thanks L. S.
Segers, PhD; B. G. Lindsey, PhD; and B. M.
Schnapf, DO, for critical review and J.D. Carver, PhD and M-F. Hutchison, MA for editorial input.
Essentials to Remember
s The upper airway plays roles in all the extended functions of breathing, namely, in airway protection, in the control of supra- and subglottic volumes, and in tidal ventilation.
s Nasal functions include air condition- ing and airway protection. Stimulation can result in profuse secretions, altered patency, and the cardiorespiratory dive reflex. Obstruction can affect gas exchange markedly; thus, a rapid switch to oral breathing is advantageous.
s Pharyngeal patency can be altered in sleep. Nonnutritive swallowing is vital to minimize aspiration. Therapy with CPAP improves pharyngeal patency in OSA but may alter pharyngeal clearing mechanisms and increase gastric air.
s Laryngeal closure can protect the air- way rapidly. Laryngospasm can be hard to treat.
s Controlled expiratory laryngeal closure modifies airflow and subglottic airway volume in normal breathing, at the establishment of airway volume at birth or when airway volume is threatened by mechanical, chemical, or central changes.
s Intrinsically or extrinsically induced changes in central state alter the laryn- geal motor outputs in response to mechanical or chemical inputs.
s Understanding how laryngeal motor functions affect breathing patterns, air- way pressures, and gas exchange is at the core of many technical and proce- dural advances in the provision of resus- citative measures and of invasive and noninvasive respiratory support.
Pediatric and Neonatal Mechanical Ventilation
4.2 Mechanics of the Lung,